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Handheld Sensor Detects Markers for Early-Stage Alzheimer’s




        

A newly-developed, handheld optical sensor could make Alzheimer’s disease easier to detect in its early stages, when treatments for the disease are most effective. The photonic resonant sensor is the result of a collaboration among researchers at the University of York, the University of Strathclyde, and the University of São Paulo.

The team developed a sensor that can simultaneously detect two of the amyloid peptides that are indicators for Alzheimer’s, at the levels clinically required for diagnosis. The capability to simultaneously detect beta amyloid 40 and beta amyloid 42 in the blood opens a route to quantifying and analyzing their ratio, enabling the progression of the disease to be tracked. Single biomarker detection is insufficient for clinical diagnosis.

Photonic resonant sensors allow for the label-free detection of specific molecules, in addition to surface imaging and the multiplexing of different biomarkers. They are compatible with low-cost fabrication processes and can be implemented with minimal optoelectronic elements for the signal readout.

Detecting peptides, however, remains a challenge for this class of sensors, mainly due to the low molecular weight of the peptides. Amyloid peptides are small and occur at low concentrations.

To ensure a high-performing sensor that could detect peptides in the blood, the researchers integrated gold nanoparticles with a dielectric nanopillar photonic crystal structure in a dimer configuration. The gold nanoparticles amplified the optical signal used to detect Alzheimer’s disease biomarkers dramatically, compared to the team’s previous sensor design, which involved the use of parallel grooves.

“This new design has allowed us to detect the amyloid biomarkers at the ultralow, clinically relevant concentrations we need, which our previous sensor couldn’t quite reach,” researcher Steven Quinn said. “The added bonus is that the technology remains scalable, mass-producible, and we aim for it to be as simple to use as a Covid test.”

The sensor design combines high resonance Q-factor, amplitude, and sensitivity, leading to a high figure of merit. “When you compare different technologies in photonics, you use a ‘figure of merit,’ which is like a scorecard that takes into account key parameters like sensitivity and signal-to-noise ratio,” Quinn said. “Our new sensor’s scorecard outperforms competing technologies.”

The sensor can detect beta amyloid 40 and beta amyloid 42 peptides in the same channel, which is relevant for assessing disease progress, and opens a route toward multiplexing. To achieve high selectivity and specificity in the sensor, the researchers used an immunoassay design approach.

The researchers are integrating the sensor technology into a handheld device. Potentially, this device could provide an indication of disease within seconds from a simple finger-prick of blood, at a projected cost of less than £100 per test. Low-cost, point-of-care testing could broaden accessibility to early Alzheimer’s testing and diagnosis, giving more patients access to treatments that are most effective in the initial stages of the disease.

“New Alzheimer’s treatments work by specifically targeting the sticky amyloid proteins that build up in the brain,” Quinn said. “For these drugs to be effective, doctors first need to confirm that a patient has this protein build-up — a condition known as amyloid positivity. A simple, scalable blood test could be the way to facilitate widespread access to these emerging treatments.”

Current methods for diagnosing Alzheimer’s disease, such as brain scans (PET/MRI) or invasive lumbar punctures, are costly, time-consuming, and are not readily accessible. Highly accurate, lab-based blood tests are now available, but they rely on large, expensive machinery, with a single test potentially costing thousands of pounds.

The next milestone for the team will be to validate the photonic sensor using blood samples from patients with Alzheimer’s and a healthy control group. This crucial phase will determine how effectively the sensor can differentiate between the two groups.

The new sensor technology could be used to detect other biomarkers and markers for other diseases. “The same principles and protocols can be used to detect a protein called phosphorylated tau, another key Alzheimer’s biomarker, as well as alpha-synuclein in Parkinson’s disease,” Quinn said. “We believe this could become a platform technology to help differentiate between various forms of dementia, which is a major challenge for clinicians.”

Although the team still needs to demonstrate the effectiveness of the sensor in patient samples, it believes that the photonic biosensor holds significant promise as a cost-effective tool to open the door to widely available testing for Alzheimer’s and other neurodegenerative diseases.

“Our vision is a device that is user-friendly for clinicians and can be deployed in healthcare settings around the world,” Quinn said.

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